Chromatography columns are typically formed of three main components, a body, a fixed bottom plate, and a movable top plate. The body is typically a hollow cylinder made of glass, acrylic or stainless steel. The bottom plate closes off the bottom of the body and typically has a screen and flow collector across its inner surface to collect fluid that passes through the column without disturbing the media that is also in the column. The bottom plate also has an outlet below the screen for the removal of the-fluid that has passed through the column.
The movable top plate, or flow distributor fits within the body and can move to a desired position above or on top of the media in the column. It too has a screen, commonly called a bed support across its face that is closest to the media, or bed. An inlet to the column is also formed through the top plate opening above the bed support into a space created between the face of the flow distributor and the bed support. The fluid then flows radially outward from the inlet and ideally passes uniformly through the bed support into the chromatography bed.
The flow direction can be reversed in most chromatography column designs, flowing through the bottom plate and exiting the top plate. Reversing the flow direction switches the utility of the top and bottom plates.
Most flow distributors contain a series of radial ribs on their face that help support the bed support and also help to spread the fluid outwardly in an even fashion across the face of the plate.
In practice, this design has several disadvantages.
As the inlet is typically centered on the face of the plate, there is a preference for the fluid to flow straight through the bed support directly below the inlet. This leads to non-uniform flow which adversely affects the performance of the column. At all but the slower velocities, this can cause the media below the inlet to be displaced creating a void in the bed which is designed to be uniform in cross section.
Current designs also use a large area of the peripheral edge to seal the bed support to the flow distributor. More than 10%, often more than 15% of the surface area of the top plate is consumed in this task. This limits the ability of the device to have even flow across its entire bed as the outer 10-15% of the bed doesn't receive direct flow. Limiting the surface area of the top plate adversely affects the column's performance while operating in the reverse flow direction.
Some columns use plastic bed supports, such as sintered polyethylene, but these incur other problems. One major problem with plastics is their inability to wet out, causing one to remove the air trapped in the pores before running the column. Likewise, any air that becomes entrapped in the bed during use is difficult to remove, as the plastic does not easily pass it through its structure. Another major problem with using plastic bed supports with the flow distributor is that they cannot and are not used on production size or large scale pilot chromatography columns without adding supports to the flow distributor which are obstructive to the flow distribution and may not be cleanable. This means that one cannot use the same design of flow distributor/bed supporting pilot and process scale applications and therefore the two designs will not be scalable thereby wasting time and money developing a separate protocol for the system.
Another disadvantage is that all of these effects are exacerbated at higher velocities. Additionally, the conventional design causes a high-pressure drop through the column at higher(greater than 100 cm/hr) velocities. High-pressure drops through the column can limit the velocity or alternatively the bed height at which the column can be safely operated.
Moreover, despite the large area used to secure the bed support to the flow distributor, at higher velocities, these bed supports have been known to detach from the flow distributor, especially plastic bed supports, or to bow outward, again creating a flow discontinuity.
One approach has been to secure the bed support at its center by a bolt that is screwed into the flow distributor. This has done little to solve the problems and creates another discontinuity in the bed as well as problems with the cleanability of the design.
In the Vantage® columns, available from Millipore Corporation of Billerica, Mass., a distribution disk has been formed so that its outer edge is mated with the inner portions of the ribs. This disk is permanently attached to the ribs.
It provides for a better flow distribution in that it reduces channeling and preferential flow down the center of the column bed. However, as it is sealed to the ribs, one now forms a series of quadrants through which fluid is divided and distributed. It still uses greater than 10% of the surface area of the flow distribution face to attach the bed support and it still cannot handle higher velocities.
What is needed is a better flow distributor design that has good flow distribution characteristics while acting as a flow distribution point or a collection point, less than about 10% of the available surface used to seal the bed support to the flow distributor and which is able to handle higher velocities with little pressure drop and without bowing or detaching the bed support.